1 Student Research Committee, Gorgan Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Golestan province, Iran (Islamic Republic of)
2 Metabolic Disorders Research Center, Department of Biochemistry and Biophysics, Gorgan Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Golestan province, Iran (Islamic Republic of)
3 Golestan Research Center of Gastroenterology and Hepatology, Gorgan Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Golestan province, Iran (Islamic Republic of)
Introduction. The role of progranulin in individuals with metabolic syndrome is not exactly clear.We aimed to assess the serum level of progranulin in type 2 diabetic patients with and without metabolic syndrome and compare them with healthy controls.
Methods. The study included 60 patients with type 2 diabetes and 30 healthy individuals as control groups. Biochemical parameters and progranulin levels were determined.
Results. Subjects with metabolic syndrome showed significantly higher levels of triglyceride, waist circumference, BMI, systolic and diastolic blood pressure than subjects without metabolic syndrome and the control groups, while HDL-cholesterol level was significantly lower in subjects with metabolic syndrome. Fasting blood sugar was significantly higher in type 2 diabetic patients than in the control groups. Serum level of progranulin was slightly increased in subjects with metabolic syndrome. Serum progranulin level had no significant relationship with metabolic syndrome components.
Conclusions. Serum progranulin was also not dependent on cardiometabolic risk factors for subjects with metabolic syndrome, but it could be considered for the management of type 2 diabetes mellitus. Further studies are recommended to explain the effect of progranulin on the pathogenesis of metabolic risk factors.
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1. MIRANDA PJ DEFRONZO RA CLIFF RM and GUYTON JR. Metabolic syndrome: definition pathophysiology and mechanisms. Am Heart J. 2005; 149: 33-45.
2. CAMERON AJ SHAW JE and ZIMMET PZ. The metabolic syndrome: prevalence in worldwide populations Endocrinol Metab Clin N Am. 2004; 33: 351-75.
3. MARJANI A HEZARKHANI S SHAHIMI N. Prevalence of metabolic syndrome among Fars ethnic Women in north east of Iran. World J Med Sci.2012; 7(1):17-22.
4. SHAHIMI N SHAHIMI I MARJANI A. Prevalence of metabolic syndrome in Turkmen ethnic groups in Gorgan. J Clin Diagn Res. 2013; 7(9):1849-51.
5. MARJANI A SHAHIMI N AGHATABAY O GHIYAS YABARI R. Prevalence of metabolic syndrome among sistanee ethnic women. Adv Stud Biol. 2012; 8(4):363-72.
6. MARJANI A SHAHIMI N. Age related metabolic syndrome among Fars ethnic women in Gorgan Iran. J Pharm Biomed Sci. 2013; 30(30):929-35.
7. MARJANI A MOGHASEMI S. The Metabolic Syndrome among Postmenopausal Women in Gorgan. Int J Endocrinol. 2012; 2012:953627.
8. GHIYAS YABARI M NASERI F PAAD E MAJIDI F MARJANI A. Prevalence of metabolic syndrome in Baluch women in Chabahar. International Journal of Osteoporosis and Metabolic Disorders. 2015; 8 (2): 27-34.
9. MARJANI A ALIAKBARI F ZAMAN KAMKAR M. Body mass index dependent metabolic syndrome in severe mental illness patients. International Journal of Osteoporosis and Metabolic Disorders. 2015; 8 (1): 19-26.
10. SHAFAEI A KHOSHNIAM MARJANI A. Serum level of fibroblast growth factor 21 in type 2 diabetic patients with and without metabolic syndrome. Journal of Medical Sciences. 2015; 15 (2): 80-86.
11. MARJANI A. A review on the role of triglyceride in metabolic syndrome. Asian Journal of Pharmaceutical and Clinical Research. 2015; 8 (3): 1-3.
12. MARJANI A. A review on the role of hypertension in the metabolic syndrome. Journal of Biological Sciences. 2013;13 (8): 685-690.
13. 13.MARJANI A MOUJERLOO M HEZARKHANI S. Age related metabolic syndrome among hemodialysis patients in Gorgan Iran. Open Biochemistry Journal. 2013: 7 (1): 15-18.
14. MARJANI A MOGHASEMI S. Serum vitamin D and metabolic syndrome among postmenopausal women in Gorgan. Biomedical Research. 2012; 23 (2): 275-280.
15. MARJANI A SHIRAFKAN A. The metabolic syndrome in type 2 diabetic patients in Gorgan: According to NCEP ATPIII and IDF definitions. Diabetes and Metabolic Syndrome: Clinical Research and Reviews. 2011; 5 (4): 207-210.
16. MARJANI A MOUJERLOO M. The metabolic syndrome in type 2 diabetic subjects in Gorgan Iran. Journal of the Pakistan Medical Association. 2011; 61 (5): 458-461.
17. ZANOCCO-MARANI T BATEMAN A ROMANO G VALENTINIS B HE ZH BASERGA R. Biological activities and signaling pathways of the granulin/epithelin precursor. Cancer Res. 1999; 59:5331-5340.
18. SHOYAB M McDONALD VL BYLES C TODARO GJ PLOWMAN GD. Epithelins 1 and 2: isolation and characterization of two cysteine rich growth-modulating proteins. Proc Natl Acad Sci. 1990; 87:7912-7916.
19. PLOWMAN GD GREEN JM NEUBAUER MG et al. The epithelin precursor encodes two proteins with opposing activities on epithelial cell growth. J Biol Chem. 1992; 267:13073-13078.
20. ANAKWE OO GERTON GL. Acrosome biogenesis begins during meiosis: evidence from the synthesis and distribution of an acrosomal glycoprotein acrogranin during guinea pig spermatogenesis. Biol Reprod. 1990; 42:317-328.
21. ZHOU J GAO G CRABB JW SERRERO G. Purification of an autocrine growth factor homologous with mouse epithelin precursor from a highly tumorigenic cell line. J Biol Chem. 1993; 268: 10863-10869.
22. DANIEL R HE Z CARMICHAEL KP HALPER J BATEMAN A. Cellular localization of gene expression for progranulin. J Histochem Cytochem. 2000; 48:999-1009.
23. LIU CJ. Progranulin: a promising therapeutic target for rheumatoid arthritis. FEBS Lett. 2011; 585: 3675-3680.
24. HE Z and BATEMAN A. Progranulin (granulin-epithelin precursor PC-cell-derived growth factor acrogranin) mediates tissue repair and tumorigenesis. Journal of Molecular Medicine. 2003; 81(10): 600-612.
25. BAKER M MACKENZIE IR PICKERING-BROWN SM GASS J RADEMAKERS R LINDHOLM C et al. Mutations in progranulin cause-negative frontotemporal dementia linked to chromosome 17. Nature. 2006; 442: 916-919.
26. CRUTS M GIJSELINCK I VAN DER ZEE J ENGELBORGHS S WILS H PIRICI D et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature. 2006; 442: 920-924.
27. DANIEL R DANIEL E HE Z BATEMAN A. Progranulin (acrogranin/PC cell-derived growth factor/granulin-epithelin precursor) is expressed in the placenta epidermis microvasculature and brain during murine development. Dev Dyn. 2003; 227:593-599.
28. MARTENS LH ZHANG J BARMADA SJ ZHOU P KAMIYA S SUN B et al. Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury. J. Clin. Invest. 2012; 122: 3955-3959.
29. AHAMED Z SHENG H XU Y-F LIN W-L INNES AE GASS J et al. Accelerated lipofuscinosis and ubiquitination in granulin knockout mice suggest a role for progranulin in successful aging. Am. J. Pathol.2010; 177: 311-324.
30. YIN F BANERJEE R THOMAS B ZHOU P QIAN L JIA T et al. Exaggerated inflammation impaired host defense and neuropathology in progranulin deficient mice. J. Exp. Med.2010; 207: 117-228.
31. TANG W LU Y TIAN Q-Y ZHANG Y GUO F-J LIU G-Y et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011; 332: 478-484.
32. COPPOLA G KARYDAS A RARMAKERS R WANG Q BAKER M HUTTON M et al. Gene expression study on peripheral blood identifies progranulin mutations. Ann. Neurol. 2008; 64: 92-96.
33. GHIDONI R BENUSSI L GLIONNA M and FRANZONI M. Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration. Neurology. 2008; 71: 1235-1239.
34. FINCH N BAKER M CROOK R SWANSON K KUNTZ K SURTEES R et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain.2009; 132: 583-591.
35. YOUN B-S BANG S-I KLOETING N PARK JW LEE N OH J-E et al. Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue. Diabetes. 2009; 58: 627-636.
36. CARECCHIO M FENOGLIO C De RIZ M GUIDI I COMI C CORTINI F et al. Progranulin plasma levels as potential biomarker for the identification of GRN deletion carriers. A case with atypical onset as clinical amnestic mild cognitive impairment converted to Alzheimer’s disease. J. Neurol. Sci. 2009; 287: 291-293.
37. HSIUNG GY FOK A FELDMAN HH RADEMAKERS R and MACKENZIE IR rs5848 polymorphism and serum progranulin level. J. Neurol. Sci. 2011; 300: 28-32.
38. ZHU J NATHAN C JIN W SIM D ASHCRFT GS WAHL SM et al. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell. 2002; 111: 867-878.
39. MATSUBARA T MITA A MINANI K HOSOOKA T KITAZAWA S TAKAHASHI K et al. PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue. Cell Metabolism. 2012; 15: 38-50.
40. [No author listed] 2001 Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) JAMA. 2001; 285: 2486-97.
41. World Health Organization. Prevention and Management of the Global Epidemic of Obesity. Report of the WHO Consultation on Obesity. WHO: Geneva (Technical Report Series No. 894) 1998.
42. RYDEN M. Fibroblast growth factor 21: an overview from a clinical perspective. Cell Mol Life Sci. 2009; 66: 2067-73.
43. OKURA H YAMASHITA S OHAMA T SAGA A YAMAMOTO-KAKUTA A HAMADA Y. et al. HDL/apolipoprotein A-I binds to macrophage-derived progranulin and suppresses its conversion into proinflammatory granulins. J. Atheroscler. Thromb. 2010; 17: 568-577.
44. NGUYEN AD NGUYEN TA CENIK B YU G HERZ J TOBIAS C et al. Secreted progranulin is a homodimer and is not a component of high density lipoproteins (HDL). The Journal of Biological Chemistry. 2013; 288(12): 8627-8635 2013.
45. YOO HJ HWANG SY HONG HC CHOI HY YANG SJ CHOI DS et al. Implication of progranulin and C1q/TNF-related protein-3 (CTRP3) on inflammation and atherosclerosis in subjects with or without metabolic syndrome. PLOS ONE. 2013; 8(2): e55744.
46. FAERCH K VAAG A WITTE DR JORGENSEN T PEDERSEN O et al. Predictors of future fasting and 2-h post-OGTT plasma glucose levels in middle-aged men and women-the Inter 99 study. Diabet Med. 2009; 26(4): 377-383.
47. QU H DENG H and HU Z. Plasma Progranulin Concentrations Are Increased in Patients with Type 2 Diabetes and Obesity and Correlated with Insulin Resistance. Mediators of Inflammation Volume 2013 Article ID 360190 6 pages.
48. ISMAIL NA RAGAB S ABD EL BAKY ANE HAMED M AYOUB DF. Relation between serum progranulin inflammatory markers and visceral fat in childhood obesity. Advances in Bioscience and Biotechnology 2013; 4: 1030-1038.
49. American Diabetes Association Classification and diagnosis of diabetes. Diabetes Care. 2015; 38:S8-S16.
50. TANAKA S TANAKA S IIMURO S YAMASHITA H KATAYAMA S AKANUMA Y et al. Predicting macro- and microvascular complications in type 2 diabetes. Diabetes Care. 2013; 36:1193-1199.
51. XU L ZHOU B LI H LIU J DU J ZANG W et al. Serum levels of progranulin are closely associated with microvascular complication in type 2 diabetes. Dis Markers. 2015; 2015: 357279.
52. ZHOU M TANG W FU Y XU X WANG Z LU Y et al. Progranulin protects against renal ischemia/reperfusion injury in mice. Kidney Int. 2015; 87:918-929.